Field of the Invention
The present invention relates to a method of deprotecting, by catalytic hydrogenation, an organic compound having a functional group protected by a protecting group.
Discussion of the Background
In the field of organic synthesis, a method of protecting a functional group by a protecting group and a method of deprotection of the protecting group are frequently used, and improvement of the reaction efficiency thereof has been desired. A benzyl group (Ph-CH2—, abbreviation Bn) and a benzhydryl group (Ph2-CH—) are frequently used as a protecting group for carboxy group, amino group and hydroxy group, further, a trityl group (Ph3-C—, abbreviation Tr) is frequently used as a protecting group for carboxy group and amino group, a benzyloxycarbonyl group (Ph-CH2O—CO—, abbreviation Cbz) is frequently used as a protecting group for amino group and hydroxy group, a 9-phenylfluorenyl group represented by the following formula is frequently used as a protecting group for amino group, and a benzyloxymethyl group (Ph-CH2O—CH2—, abbreviation Bom) is frequently used as a protecting group for the amino group of an imidazole ring possessed by histidine and the like.
A functional group protected by the aforementioned protecting group containing a structure represented by the formula: Ar—C— wherein Ar is an aryl group) (hereinafter sometimes to be abbreviated as “benzyl-type protecting group”) is generally deprotected by catalytic hydrogenation using a metal catalyst (e.g., palladium catalyst, platinum catalyst etc.) under a hydrogen atmosphere. In this deprotection, it is considered that (1) first, a benzyl-type protecting group is trapped on a surface of the metal catalyst by an interaction between an aryl group and a metal catalyst, (2) then, cleavage of the benzyl-type protecting group and the functional group (e.g., carboxy group) proceeds due to catalytic hydrogenation on the surface of the metal catalyst.
The catalyst activity of a metal catalyst is markedly impaired by a catalyst poison present in situ. As such catalyst poison, a sulfur-containing organic compound is typical. Therefore, it is generally difficult to deprotect, by catalytic hydrogenation, a sulfur-containing organic compound having a functional group protected by a benzyl-type protecting group.
Non-patent document 1 describes that, in catalytic hydrogenation (metal catalyst: palladium carbon) of a substrate having an amino group protected by Cbz and a double bond, selective catalytic hydrogenation of the double bond alone is performed by adding diphenylsulfide in situ, without deprotecting Cbz.
Non-patent document 2 describes deprotection of Cbz, as shown in the following formula, by refluxing a sulfur-containing peptide having the N-terminus protected by Cbz together with palladium black and triethylamine in dimethylacetamide (DMAC) and liquid ammonia under a hydrogen stream. However, in the method described in non-patent document 2, an excess amount of palladium black is used in about 5 equivalents or 15 equivalents relative to the substrate to avoid an influence of catalyst poison.
